JPH0822865B2 - フェノール置換ジェム―ジホスホネート誘導体、その調製法およびそれを含む医薬組成物 - Google Patents
フェノール置換ジェム―ジホスホネート誘導体、その調製法およびそれを含む医薬組成物Info
- Publication number
- JPH0822865B2 JPH0822865B2 JP1083855A JP8385589A JPH0822865B2 JP H0822865 B2 JPH0822865 B2 JP H0822865B2 JP 1083855 A JP1083855 A JP 1083855A JP 8385589 A JP8385589 A JP 8385589A JP H0822865 B2 JPH0822865 B2 JP H0822865B2
- Authority
- JP
- Japan
- Prior art keywords
- diphosphonate
- butyl
- hydroxyphenyl
- tetraethyl
- tert
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 238000002360 preparation method Methods 0.000 title description 4
- 239000008194 pharmaceutical composition Substances 0.000 title description 3
- -1 alkylidene diphosphonate Chemical class 0.000 claims description 56
- 239000003814 drug Substances 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- ISLWZBTUAHMAND-UHFFFAOYSA-N 1,3,2-dioxaphosphinan-2-ium 2-oxide Chemical compound O=[P+]1OCCCO1 ISLWZBTUAHMAND-UHFFFAOYSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 150000002500 ions Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
- JZEYKVNRHUIKBF-UHFFFAOYSA-N [(3,5-ditert-butyl-4-hydroxyphenyl)sulfanyl-phosphonomethyl]phosphonic acid Chemical compound CC(C)(C)C1=CC(SC(P(O)(O)=O)P(O)(O)=O)=CC(C(C)(C)C)=C1O JZEYKVNRHUIKBF-UHFFFAOYSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 150000007513 acids Chemical class 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- 150000001875 compounds Chemical class 0.000 description 46
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- 239000000203 mixture Substances 0.000 description 28
- 239000000243 solution Substances 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- 125000003118 aryl group Chemical group 0.000 description 18
- 238000004440 column chromatography Methods 0.000 description 17
- 238000005481 NMR spectroscopy Methods 0.000 description 16
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 16
- 229910004298 SiO 2 Inorganic materials 0.000 description 12
- 230000008018 melting Effects 0.000 description 11
- 238000002844 melting Methods 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 10
- 238000000034 method Methods 0.000 description 9
- XCXJLWLQQPJVDR-UHFFFAOYSA-N 3-(azepan-2-yl)quinoline Chemical compound C1CCCCNC1C1=CN=C(C=CC=C2)C2=C1 XCXJLWLQQPJVDR-UHFFFAOYSA-N 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- 238000000921 elemental analysis Methods 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 150000002632 lipids Chemical class 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 208000029078 coronary artery disease Diseases 0.000 description 5
- XQRLCLUYWUNEEH-UHFFFAOYSA-L diphosphonate(2-) Chemical compound [O-]P(=O)OP([O-])=O XQRLCLUYWUNEEH-UHFFFAOYSA-L 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 229940126639 Compound 33 Drugs 0.000 description 4
- 206010020772 Hypertension Diseases 0.000 description 4
- PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000036772 blood pressure Effects 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- DOZRDZLFLOODMB-UHFFFAOYSA-N 3,5-di-tert-Butyl-4-hydroxybenzaldehyde Chemical compound CC(C)(C)C1=CC(C=O)=CC(C(C)(C)C)=C1O DOZRDZLFLOODMB-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 206010030113 Oedema Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 235000012000 cholesterol Nutrition 0.000 description 3
- 229940125898 compound 5 Drugs 0.000 description 3
- 239000013256 coordination polymer Substances 0.000 description 3
- XQRLCLUYWUNEEH-UHFFFAOYSA-N diphosphonic acid Chemical compound OP(=O)OP(O)=O XQRLCLUYWUNEEH-UHFFFAOYSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 3
- 229960002297 fenofibrate Drugs 0.000 description 3
- 210000002683 foot Anatomy 0.000 description 3
- 229960003627 gemfibrozil Drugs 0.000 description 3
- 150000002431 hydrogen Chemical group 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 229910052697 platinum Inorganic materials 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000000526 short-path distillation Methods 0.000 description 3
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 3
- MDTMOBMECRUULW-UHFFFAOYSA-J tetrasodium;dioxido-oxo-(phosphonatomethyl)-$l^{5}-phosphane Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)CP([O-])([O-])=O MDTMOBMECRUULW-UHFFFAOYSA-J 0.000 description 3
- KPZGRMZPZLOPBS-UHFFFAOYSA-N 1,3-dichloro-2,2-bis(chloromethyl)propane Chemical compound ClCC(CCl)(CCl)CCl KPZGRMZPZLOPBS-UHFFFAOYSA-N 0.000 description 2
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 2
- NFVMNXZFSKGLDR-UHFFFAOYSA-N 2,6-ditert-butyl-4-sulfanylphenol Chemical compound CC(C)(C)C1=CC(S)=CC(C(C)(C)C)=C1O NFVMNXZFSKGLDR-UHFFFAOYSA-N 0.000 description 2
- YEOQCOZNFXPHHY-UHFFFAOYSA-N 4-(bromomethyl)-2,6-ditert-butylphenol Chemical compound CC(C)(C)C1=CC(CBr)=CC(C(C)(C)C)=C1O YEOQCOZNFXPHHY-UHFFFAOYSA-N 0.000 description 2
- DOJDZINFSHQKOG-UHFFFAOYSA-N 4-[bis(diethoxyphosphoryl)methylsulfanyl]-2,6-ditert-butylphenol Chemical compound CCOP(=O)(OCC)C(P(=O)(OCC)OCC)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 DOJDZINFSHQKOG-UHFFFAOYSA-N 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- 208000001953 Hypotension Diseases 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- ZNOZWUKQPJXOIG-XSBHQQIPSA-L [(2r,3s,4r,5r,6s)-6-[[(1r,3s,4r,5r,8s)-3,4-dihydroxy-2,6-dioxabicyclo[3.2.1]octan-8-yl]oxy]-4-[[(1r,3r,4r,5r,8s)-8-[(2s,3r,4r,5r,6r)-3,4-dihydroxy-6-(hydroxymethyl)-5-sulfonatooxyoxan-2-yl]oxy-4-hydroxy-2,6-dioxabicyclo[3.2.1]octan-3-yl]oxy]-5-hydroxy-2-( Chemical compound O[C@@H]1[C@@H](O)[C@@H](OS([O-])(=O)=O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H]2OC[C@H]1O[C@H](O[C@H]1[C@H]([C@@H](CO)O[C@@H](O[C@@H]3[C@@H]4OC[C@H]3O[C@H](O)[C@@H]4O)[C@@H]1O)OS([O-])(=O)=O)[C@@H]2O ZNOZWUKQPJXOIG-XSBHQQIPSA-L 0.000 description 2
- PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
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- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
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- MBKDYNNUVRNNRF-UHFFFAOYSA-N medronic acid Chemical compound OP(O)(=O)CP(O)(O)=O MBKDYNNUVRNNRF-UHFFFAOYSA-N 0.000 description 2
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
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- 230000000144 pharmacologic effect Effects 0.000 description 2
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 2
- SATCULPHIDQDRE-UHFFFAOYSA-N piperonal Chemical compound O=CC1=CC=C2OCOC2=C1 SATCULPHIDQDRE-UHFFFAOYSA-N 0.000 description 2
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- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
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- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
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- 150000003626 triacylglycerols Chemical class 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3839—Polyphosphonic acids
- C07F9/386—Polyphosphonic acids containing hydroxy substituents in the hydrocarbon radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3839—Polyphosphonic acids
- C07F9/3865—Polyphosphonic acids containing sulfur substituents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4025—Esters of poly(thio)phosphonic acids
- C07F9/404—Esters of poly(thio)phosphonic acids containing hydroxy substituents in the hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4025—Esters of poly(thio)phosphonic acids
- C07F9/4043—Esters of poly(thio)phosphonic acids containing sulfur substituents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/44—Amides thereof
- C07F9/4403—Amides thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4423—Amides of poly (thio)phosphonic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/65515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring
- C07F9/65517—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring condensed with carbocyclic rings or carbocyclic ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
- C07F9/657163—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms the ring phosphorus atom being bound to at least one carbon atom
- C07F9/657181—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms the ring phosphorus atom being bound to at least one carbon atom the ring phosphorus atom and, at least, one ring oxygen atom being part of a (thio)phosphonic acid derivative
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Medicinal Chemistry (AREA)
- Diabetes (AREA)
- Engineering & Computer Science (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1239/88A CH675422A5 (he) | 1988-03-31 | 1988-03-31 | |
| CH1239/88 | 1988-03-31 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0222285A JPH0222285A (ja) | 1990-01-25 |
| JPH0822865B2 true JPH0822865B2 (ja) | 1996-03-06 |
Family
ID=4205733
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1083855A Expired - Fee Related JPH0822865B2 (ja) | 1988-03-31 | 1989-03-31 | フェノール置換ジェム―ジホスホネート誘導体、その調製法およびそれを含む医薬組成物 |
Country Status (25)
| Country | Link |
|---|---|
| US (2) | US5043330A (he) |
| EP (1) | EP0339237B1 (he) |
| JP (1) | JPH0822865B2 (he) |
| KR (1) | KR0147830B1 (he) |
| CN (2) | CN1024555C (he) |
| AR (1) | AR247569A1 (he) |
| AT (1) | ATE84040T1 (he) |
| AU (1) | AU612475B2 (he) |
| CA (1) | CA1338495C (he) |
| CH (1) | CH675422A5 (he) |
| DE (2) | DE339237T1 (he) |
| DK (1) | DK173936B1 (he) |
| ES (1) | ES2011210T3 (he) |
| FI (1) | FI92933C (he) |
| GR (2) | GR900300002T1 (he) |
| HU (1) | HU203556B (he) |
| IE (1) | IE62692B1 (he) |
| IL (1) | IL89649A (he) |
| MY (1) | MY103850A (he) |
| NO (1) | NO891317L (he) |
| NZ (1) | NZ228516A (he) |
| PH (1) | PH27603A (he) |
| PT (1) | PT90175B (he) |
| ZA (1) | ZA892126B (he) |
| ZW (1) | ZW3789A1 (he) |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0377894A (ja) * | 1989-08-18 | 1991-04-03 | Toray Ind Inc | メチレンジホスホン酸化合物 |
| JPH05163150A (ja) * | 1991-05-13 | 1993-06-29 | E R Squibb & Sons Inc | アテローム性動脈硬化症の抑制・治療剤 |
| US5157027A (en) * | 1991-05-13 | 1992-10-20 | E. R. Squibb & Sons, Inc. | Bisphosphonate squalene synthetase inhibitors and method |
| CA2067974A1 (en) * | 1991-05-13 | 1992-11-14 | Scott A. Biller | Method for lowering cholesterol employing a phosphonomethylphosphinate squalene synthetase inhibitor |
| DK0594857T3 (da) * | 1991-09-05 | 1998-10-07 | Toray Industries | Methandiphosphonsyrederivat, fremstilling deraf ogmedicinsk anvendelse deraf |
| EP0541037A3 (en) * | 1991-11-06 | 1997-02-26 | Takeda Chemical Industries Ltd | Squalene synthetase inhibitory composition and use thereof |
| JPH06172372A (ja) * | 1991-11-06 | 1994-06-21 | Takeda Chem Ind Ltd | スクアレン合成酵素阻害剤およびその用途 |
| FR2683529B1 (fr) * | 1991-11-12 | 1994-02-04 | Bretagne Occidentale Universite | Composes pharmaceutiques gem-diphosphonates analogues du cis-platine. |
| CH683996A5 (fr) * | 1992-03-05 | 1994-06-30 | Symphar Sa | Dérivés aminophosphonates substitués, leur procédé de préparation et compositions pharmaceutiques les contenant. |
| DE69330114T2 (de) * | 1992-07-10 | 2001-08-02 | Toray Industries, Inc. | Methandiphosphonat-derivat, dessen produktion und dessen verwendung als arzneimittel |
| US5332728A (en) * | 1992-11-23 | 1994-07-26 | Bristol-Myers Squibb Company | Method for treating a fungal infection |
| US5434288A (en) * | 1992-12-01 | 1995-07-18 | Monsanto Company | PLA2 inhibitors |
| ZA941088B (en) * | 1993-02-19 | 1995-09-27 | Symphar Sa | Substituted ketophosphonates the processes for their preparation and pharmaceutical compositions containing them |
| AU674059B2 (en) * | 1993-02-25 | 1996-12-05 | Toray Industries, Inc. | Process for producing methanediphosphonate compound |
| US5419845A (en) * | 1994-03-15 | 1995-05-30 | Basf Corporation | Perfluorinated gemdiphosphonates as corrosion inhibitors for antifreeze coolants and other functional fluids |
| ATE235499T1 (de) * | 1994-08-24 | 2003-04-15 | Toray Industries | Verfahren zur herstellung einer methanphosphonsäureverbindung |
| CH690163A5 (fr) * | 1995-07-28 | 2000-05-31 | Symphar Sa | Dérivés gem-diphosphonates substitués utiles en tant qu'agents anti-cancers. |
| GB9603637D0 (en) * | 1996-02-21 | 1996-04-17 | Smithkline Beecham Plc | Process |
| EP0952834A2 (en) * | 1996-05-15 | 1999-11-03 | The University of Sheffield | Isopentenyl pyrophosphate isomerase (ipi) and/or prenyl transferase inhibitors |
| US6670398B2 (en) * | 1997-05-14 | 2003-12-30 | Atherogenics, Inc. | Compounds and methods for treating transplant rejection |
| EA009987B1 (ru) * | 1997-05-14 | 2008-04-28 | Атеродженикс, Инк. | Производные пробукола для лечения заболеваний, опосредованных vcam-1 |
| US7008645B2 (en) | 1998-07-14 | 2006-03-07 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Method of inhibiting restenosis using bisphosphonates |
| IL125336A0 (en) * | 1998-07-14 | 1999-03-12 | Yissum Res Dev Co | Compositions for inhibition and treatment of restinosis |
| US6984400B2 (en) | 1998-07-14 | 2006-01-10 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Method of treating restenosis using bisphosphonate nanoparticles |
| AUPQ872800A0 (en) * | 2000-07-12 | 2000-08-03 | Heart Research Institute, The | Compositions and methods for treating cardiovascular disorders |
| GB0019272D0 (en) * | 2000-08-04 | 2000-09-27 | Symphar Sa | Pharmaceutical compounds |
| WO2002087556A2 (en) * | 2001-04-11 | 2002-11-07 | Atherogenics, Inc. | Probucol monoesters and their use to increase plasma hdl cholesterol levels and improve hdl functionality |
| EP1435970A4 (en) * | 2001-10-18 | 2005-05-04 | Ilex Products Inc | METHOD OF TREATING SKIN WITH DIPHOSPHONATE DERIVATIVES |
| EP1485106A2 (en) * | 2002-02-19 | 2004-12-15 | Ilex Products, Inc. | Phosphonate-phosphate and diphosphonate apolipoprotein e modulators |
| US20060205692A1 (en) * | 2002-05-11 | 2006-09-14 | Montes Imber F | 1,1-and 1,2-Bisphosphonates as apoliprotein e modulators |
| WO2004064781A2 (en) * | 2003-01-14 | 2004-08-05 | Adam Heller | Anti-inflammatory substituted phenols and elastomeric compositions for oral delivery of drugs |
| US10517883B2 (en) | 2003-06-27 | 2019-12-31 | Zuli Holdings Ltd. | Method of treating acute myocardial infarction |
| CA2646334A1 (en) * | 2006-03-17 | 2007-09-27 | The Board Of Trustees Of The University Of Illinois | Bisphosphonate compounds and methods |
| US8252840B2 (en) * | 2007-03-26 | 2012-08-28 | Salutria Pharmaceuticals Llc | Methods of derivatives of probucol for the treatment of type II diabetes |
| US20080280985A1 (en) * | 2007-03-27 | 2008-11-13 | Scott Robert A D | Methods and Compositions Using Certain Phenolic Derivatives for the Treatment of Diabetes |
| US9993427B2 (en) | 2013-03-14 | 2018-06-12 | Biorest Ltd. | Liposome formulation and manufacture |
| EP3209671B8 (en) * | 2014-10-21 | 2019-07-31 | Council of Scientific and Industrial Research | Alkylidene phosphonate esters as p-glycoprotein inducers |
| WO2018236221A2 (en) * | 2017-06-03 | 2018-12-27 | Can Holding B.V. | DISSOLUTION OF NEURODEGENERATIVE PEPTIDE DEPOSITION |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA777769A (en) * | 1963-03-18 | 1968-02-06 | H. Roy Clarence | Substituted methylene diphosphonic acid compounds and detergent compositions |
| DE1302557B (he) * | 1963-04-09 | 1971-08-26 | ||
| GB2043072B (en) * | 1979-02-13 | 1983-11-23 | Symphar Sa | Diphosphonate compounds |
| US4416877A (en) * | 1979-02-13 | 1983-11-22 | Symphar S.A. | Anti-atherosclerotic pharmaceutical compositions containing diphosphonate compounds |
| FR2531088B1 (fr) * | 1982-07-29 | 1987-08-28 | Sanofi Sa | Produits anti-inflammatoires derives de l'acide methylenediphosphonique et leur procede de preparation |
| CH664158A5 (fr) * | 1984-07-18 | 1988-02-15 | Symphar Sa | Derives propylidenediphosphonates-1,3 substitues en position 2, leur procede de preparation et compositions pharmaceutiques les contenant. |
| US6259935B1 (en) * | 1997-06-24 | 2001-07-10 | Matsushita Electrical Industrial Co., Ltd. | Electro-mechanical-acoustic transducing device |
-
1988
- 1988-03-31 CH CH1239/88A patent/CH675422A5/fr not_active IP Right Cessation
-
1989
- 1989-03-13 IE IE80289A patent/IE62692B1/en not_active IP Right Cessation
- 1989-03-14 US US07/323,334 patent/US5043330A/en not_active Expired - Lifetime
- 1989-03-15 ZW ZW37/89A patent/ZW3789A1/xx unknown
- 1989-03-16 ES ES89104656T patent/ES2011210T3/es not_active Expired - Lifetime
- 1989-03-16 DE DE198989104656T patent/DE339237T1/de active Pending
- 1989-03-16 EP EP89104656A patent/EP0339237B1/en not_active Expired - Lifetime
- 1989-03-16 MY MYPI89000332A patent/MY103850A/en unknown
- 1989-03-16 DE DE8989104656T patent/DE68904104T2/de not_active Expired - Fee Related
- 1989-03-16 AT AT89104656T patent/ATE84040T1/de not_active IP Right Cessation
- 1989-03-17 IL IL8964989A patent/IL89649A/he not_active IP Right Cessation
- 1989-03-21 ZA ZA892126A patent/ZA892126B/xx unknown
- 1989-03-22 CA CA000594468A patent/CA1338495C/en not_active Expired - Fee Related
- 1989-03-28 DK DK198901481A patent/DK173936B1/da not_active IP Right Cessation
- 1989-03-29 NZ NZ228516A patent/NZ228516A/en unknown
- 1989-03-29 AR AR89313527A patent/AR247569A1/es active
- 1989-03-29 NO NO89891317A patent/NO891317L/no unknown
- 1989-03-30 CN CN89101830A patent/CN1024555C/zh not_active Expired - Fee Related
- 1989-03-30 FI FI891538A patent/FI92933C/fi not_active IP Right Cessation
- 1989-03-30 HU HU891595A patent/HU203556B/hu not_active IP Right Cessation
- 1989-03-30 CN CN93116289A patent/CN1086820A/zh active Pending
- 1989-03-30 KR KR1019890004076A patent/KR0147830B1/ko not_active IP Right Cessation
- 1989-03-30 AU AU32243/89A patent/AU612475B2/en not_active Ceased
- 1989-03-30 PT PT90175A patent/PT90175B/pt not_active IP Right Cessation
- 1989-03-31 JP JP1083855A patent/JPH0822865B2/ja not_active Expired - Fee Related
- 1989-03-31 PH PH38417A patent/PH27603A/en unknown
-
1991
- 1991-06-07 GR GR90300002T patent/GR900300002T1/el unknown
- 1991-07-31 US US07/738,430 patent/US5128331A/en not_active Expired - Lifetime
-
1993
- 1993-03-23 GR GR930400629T patent/GR3007442T3/el unknown
Non-Patent Citations (1)
| Title |
|---|
| ＴＥＴＲＡＨＥＤＲＯＮ，ｖｏｌ．３０，ｐ．３０１〜３０５（１９７４） |
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